Anti-Thrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC): Study design and methodology for an international, adaptive Bayesian randomized controlled trial

Brett L. Houston, Patrick R. Lawler, Ewan C. Goligher, Michael E. Farkouh, Charlotte Bradbury, Marc Carrier, Vlad Dzavik, Dean A. Fergusson, Robert A. Fowler, Jean Phillippe Galanaud, Peter L. Gross, Emily G. McDonald, Mansoor Husain, Susan R. Kahn, Anand Kumar, John Marshall, Srinivas Murthy, Arthur S. Slutsky, Alexis F. Turgeon, Scott M. BerryRobert S. Rosenson, Jorge Escobedo, Jose C. Nicolau, Lindsay Bond, Bridget Anne Kirwan, Sophie de Brouwer, Ryan Zarychanski

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Background: Mortality from COVID-19 is high among hospitalized patients and effective therapeutics are lacking. Hypercoagulability, thrombosis and hyperinflammation occur in COVID-19 and may contribute to severe complications. Therapeutic anticoagulation may improve clinical outcomes through anti-thrombotic, anti-inflammatory and anti-viral mechanisms. Our primary objective is to evaluate whether therapeutic-dose anticoagulation with low-molecular-weight heparin or unfractionated heparin prevents mechanical ventilation and/or death in patients hospitalized with COVID-19 compared to usual care. Methods: An international, open-label, adaptive randomized controlled trial. Using a Bayesian framework, the trial will declare results as soon as pre-specified posterior probabilities for superiority, futility, or harm are reached. The trial uses response-adaptive randomization to maximize the probability that patients will receive the more beneficial treatment approach, as treatment effect information accumulates within the trial. By leveraging a common data safety monitoring board and pooling data with a second similar international Bayesian adaptive trial (REMAP-COVID anticoagulation domain), treatment efficacy and safety will be evaluated as efficiently as possible. The primary outcome is an ordinal endpoint with three possible outcomes based on the worst status of each patient through day 30: no requirement for invasive mechanical ventilation, invasive mechanical ventilation or death. Conclusion: Using an adaptive trial design, the Anti-Thrombotic Therapy To Ameliorate Complications of COVID-19 trial will establish whether therapeutic anticoagulation can reduce mortality and/or avoid the need for mechanical ventilation in patients hospitalized with COVID-19. Leveraging existing networks to recruit sites will increase enrollment and mitigate enrollment risk in sites with declining COVID-19 cases.

Original languageEnglish
Pages (from-to)491-500
Number of pages10
JournalClinical Trials
Issue number5
StatePublished - 1 Oct 2020


  • COVID-19
  • Heparin
  • adaptive clinical trial
  • protocol
  • thrombosis


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